The objective of this project is to combine anisotropic computational modeling with in vivo intravascular ultrasound (IVUS), angiography, ex vivo Magnetic Resonance Imaging (MRI), mechanical testing, and pathohistological analysis to analyze vulnerable atherosclerotic coronary plaques and identify critical blood flow and plaque stress/strain indicators for quantitative coronary plaque vulnerability assessment. The long term goals are: a) develop computational mechanical image analysis tools for more accurate plaque assessment and possible quantitative improvement to the current American Heart Association (AHA) plaque classification scheme; b) identify critical flow and stress/strain plaque vulnerability risk indicators which could be monitored for early prediction, diagnosis, treatment, and prevention of related cardiovascular diseases. The hypotheses are: (1) Critical plaque stress/strain conditions correlate closely with plaque vulnerability and may be used as indicators to further differentiate plaques within AHA advanced plaque classifications (types V- VIII) and provide more quantitative methods to assess plaque rupture risk; (2) Combination of in vivo IVUS imaging, pressure and flow measurements and 3D anisotropic multi-component models with fluid-structure interactions (FSI) and cyclic bending will improve the accuracy of mechanical analysis for coronary plaques and lead to more accurate in vivo plaque vulnerability assessment. This project has four specific aims. Aim 1: Develop and integrate in vivo IVUS imaging, flow and pressure measurements techniques, angiography, multi-contrast ex vivo MRI, histological analysis, and biaxial mechanical testing techniques to quantify plaque morphology, tissue components, curvature, intra-coronary flow and pressure conditions at the lesion site, and anisotropic vessel material properties. Aim 2: Develop 3D anisotropic multi-component FSI models for 100 human coronary plaques (50 in vivo IVUS, 50 ex vivo MRI) with cyclic bending and intra-coronary flow and pressure conditions (IVUS only) to obtain 3D flow shear stress and plaque stress/strain data; Aim 3: perform 3D mechanical image analysis for coronary plaques and identify correlations between critical stress/strain conditions (potential risk indicators) and plaque morphology and composition, vessel mechanical properties and blood flow pressure conditions (patient data). Computational models will be validated by both in vivo IVUS and in vitro experimental data. Aim 4: Introduce quantitative in vivo/ex vivo/histological plaque vulnerability assessment schemes and compare with AHA histology-based plaque classifications for possible quantitative improvements on AHA scheme and potential screening practice. Success of this project will lead to more accurate plaque vulnerability assessment and predictions for possible plaque rupture risk so that better decisions for treatment can be made leading to better public health and reduced costs of Medicare. Mechanical image analysis and software additions to enhance MRI/IVUS imaging technology for clinical applications are possible with future large-scale patient study validations.